Alidjinou E K, Engelmann I, Bossu J, Villenet C, Figeac M, Romond M-B, Sané F, Hober D
a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
b Plate-forme de Génomique Fonctionnelle et Structurale , CHU de Lille , France.
Virulence. 2017 Oct 3;8(7):1229-1244. doi: 10.1080/21505594.2017.1284735. Epub 2017 Jan 23.
Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated.
A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome.
The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR.
Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.
虽然B组柯萨奇病毒（CVB）被认为是溶细胞性病毒，但它们能够在体外和体内建立持续性感染。病毒持续性已被报道为CVB相关慢性疾病（如1型糖尿病（T1D））发病机制中的关键机制。研究了CVB4持续性感染对人胰腺导管样细胞的影响。
在导管样细胞中建立CVB4持续性感染。评估PDX-1表达、对CVB4诱导的裂解的抗性和CAR表达。通过miRNA测序研究细胞微小RNA（miRNA）的谱。检查病毒表型变化，并通过病毒基因组测序评估基因组修饰。
CVB4在导管样细胞中的持续性感染是有生产性的，有传染性颗粒的持续释放。持续感染的细胞在再次感染时对CVB4诱导的裂解表现出抗性，并且PDX-1和CAR的表达降低。即使在病毒清除后，这些变化仍得以维持。模拟感染和CVB4持续感染的导管样细胞中细胞miRNA表达模式明显不同。持续感染衍生病毒（PIDV）仍能诱导细胞病变效应，但其噬斑比亲代病毒小。在PIDV基因组的各个区域出现了几个突变，但氨基酸替换不影响与CAR预测的相互作用位点。
CVB4持续感染人胰腺导管样细胞期间会发生细胞和病毒变化。即使在病毒清除后细胞变化仍持续存在，这支持了CVB持续感染对细胞有长期影响的假说。
